The overall aim of this project is to develop a molecular specific autologous bone marrow transplantation (ABMT) program employing ribozymes for the treatment of Philadelphia chromosome positive chronic myelogenous leukemia (CML). We have recently developed vectors which express ribozyme molecules that cleave BCR-ABL transcripts produced in Ph-positive CML cells. This project will include: the production and packaging of a triple-unit ribozyme; establishing the incubation conditions for efficient delivery of the ribozyme by liposomes, receptor mediated delivery, and retroviral vectors; demonstration of the elimination of BCR-ABL mRNA and kinase activity from established cell lines and human bone marrow; and demonstrating reversal of the transformed phenotype in cell culture and a CML/SCID mouse model once the preclinical studies have established the optimal purging conditions employing the anti-BCR ABL triple-unit ribozyme and the details of the purging method with ribozymes have been worked out, a phase I, II clinical trial will begin. The essentials of the clinical trial will involve chronic phase CML patients without an allogeneic donor. A standard myeloablative conditioning regimen will be employed after a hone marrow or stem cell apheresis progRam. Back-up unpurged marrow or stem cells will be available in the event of a failure to engraft with ribozyme purged stem cell enriched populations.